Decreases in activated caspase-1 levels are integral to improvement of metabolic profile after laparoscopic bariatric surgery – Preliminary Report of changes in caspase-1 and mitochondrial respiration after laparoscopic bariatric surgery

S Nijhawan, MD, Diego Alvarez, MD, PhD, Jon Audia, PhD, William O Richards, MD

University of South Alabama, Mobile, AL

INTRODUCTION –Chronic, low-grade metabolic inflammation (‘meta’-inflammation) and impaired mitochondrial function is found in patients with morbid obesity and metabolic syndrome. Caspase-1 elicits inflammation via activation of selected interleukins that are typically elevated in morbidly obese patients. However, associations between caspase-1, mitochondrial respiration, and surgically induced weight loss are unknown. The goal of this study is to measure caspase-1 and mitochondrial respiration in peripheral blood monocytes and skeletal muscle from a cohort of morbidly obese patients undergoing laparoscopic bariatric surgery.

METHODS AND PROCEDURES – This is an IRB approved prospective study involving morbidly obese patients (Body mass index/BMI >35) undergoing laparoscopic bariatric surgery (sleeve gastrectomy or roux-en-y gastric bypass). A cohort of healthy individuals was used for comparison and to account for any confounding variables. Levels of activated caspase-1 were measured by intracellular staining and flow cytometry in circulating monocytes using an irreversible, fluorescently labeled caspase-1 substrate (FLICA). An oxygraph O2K polarographic high-resolution respirometer was used to measure mitochondrial respiration (JO2) in peripheral blood monocytes and skeletal muscle.

RESULTS – Mean pre-operative weight was 381.7. Mean pre-operative BMI was 63.8. Mean caspase-1 levels in patients with normal BMI as demonstrated by FLICA was 7.75 Relative Fluorescent Units (RFUs). Pre-operative activated caspase -1 level in one of our morbidly obese patients (BMI 70.3) was 28.3 RFUs. Activated caspase-1 levels in this patient dropped to 6.6 RFUs and 3.1 RFUs at 6 weeks and 12 weeks post-op, respectively. Pre-operative skeletal muscle JO2 was at the limit of detection and improved to 52 nmol/s/mg tissue/mL at 3-months post-op. Monocyte JO2 also increased from the limit of detection to 4.7 pmol/s/million cells/ml at 3-months post-op. These post-op levels were comparable to those observed in healthy, normal weight control individuals assayed in previous studies in our lab.

CONCLUSION – This study is the first report demonstrating decreased activated caspase-1 levels and resolution of monocyte and tissue mitochondrial respiration after laparoscopic bariatric surgery in a morbidly obese patient cohort. Importantly, these trends may represent critical parameters that positively impact improvement of metabolic profile in the morbidly obese patient after surgically induced weight loss.

Session: Podium Presentation

Program Number: S010

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